Accuracy of Pulse Oximetry in Children

Transcription

1 Accuracy of Pulse Oximetry in Children WHAT S KNOWN ON THIS SUBJECT: Saturations from pulse oximetry (SpO 2 ) may overestimate arterial oxygen saturations measured by CO-oximetry (SaO 2 ). The overestimation can be affected by location of measurement, perfusion, and skin color. Previous studies are limited by small numbers of observations in a hypoxemic range. WHAT THIS STUDY ADDS: This large sample of hypoxemic patients identified that SpO 2 typically overestimates SaO 2. Bias and precision varied throughout the SpO 2 range. The SpO 2 range of 81% to 85% had the greatest bias: median SpO 2 6% higher than SaO 2 measured by CO-oximetry. abstract OBJECTIVE: For children with cyanotic congenital heart disease or acute hypoxemic respiratory failure, providers frequently make decisions based on pulse oximetry, in the absence of an arterial blood gas. The study objective was to measure the accuracy of pulse oximetry in the saturations from pulse oximetry (SpO 2 ) range of 65% to 97%. METHODS: This institutional review board approved prospective, multicenter observational study in 5 PICUs included 225 mechanically ventilated children with an arterial catheter. With each arterial blood gas sample, SpO 2 from pulse oximetry and arterial oxygen saturations from CO-oximetry (SaO 2 ) were simultaneously obtained if the SpO 2 was #97%. RESULTS: The lowest SpO 2 obtained in the study was 65%. In the range of SpO 2 65% to 97%, 1980 simultaneous values for SpO 2 and SaO 2 were obtained. The bias (SpO 2 SaO 2 ) varied through the range of SpO 2 values. The bias was greatest in the SpO 2 range 81% to 85% (336 samples, median 6%, mean 6.6%, accuracy root mean squared 9.1%). SpO 2 measurements were close to SaO 2 in the SpO 2 range 91% to 97% (901 samples, median 1%, mean 1.5%, accuracy root mean squared 4.2%). CONCLUSIONS: Previous studies on pulse oximeter accuracy in children present a single number for bias. This study identified that the accuracy of pulse oximetry varies significantly as a function of the SpO 2 range. Saturations measured by pulse oximetry on average overestimate SaO 2 from CO-oximetry in the SpO 2 range of 76% to 90%. Better pulse oximetry algorithms are needed for accurate assessment of children with saturations in the hypoxemic range. Pediatrics 2014;133:22 29 AUTHORS: Patrick A. Ross, MD, Christopher J.L. Newth, MD, FRCPC, and Robinder G. Khemani, MD, MsCI Children s Hospital Los Angeles and University of Southern California Keck School of Medicine, Department of Anesthesiology Critical Care Medicine, Los Angeles, California KEY WORDS oximetry, hypoxia, heart defects, congenital heart disease/ defects, pediatric, mechanical ventilation ABBREVIATIONS ABG arterial blood gas ABG/SpO 2 pairs simultaneous measurement of ABG and SpO 2 AHRF acute hypoxemic respiratory failure A rms accuracy root mean squared CCHD cyanotic congenital heart disease FDA US Food and Drug Administration SaO 2 arterial oxygen saturations from CO-oximetry SpO 2 saturations from pulse oximetry Dr Ross participated in data collection locally, performed data analysis, and drafted and revised the manuscript for important intellectual content; Dr Newth conceptualized and designed the study and reviewed and revised the manuscript for important intellectual content; Dr Khemani conceptualized and designed the study, coordinated the data collection at 5 sites, participated in data collection locally, performed data analysis, and drafted and revised the manuscript for important intellectual content; and all authors approved the final manuscript as submitted. doi: /peds Accepted for publication Oct 3, 2013 Address correspondence to Patrick A. Ross, MD, Department of Anesthesiology Critical Care Medicine, 4650 Sunset Blvd Mailstop 12, Children s Hospital Los Angeles, Los Angeles, CA pross@chla.usc.edu PEDIATRICS (ISSN Numbers: Print, ; Online, ). Copyright 2014 by the American Academy of Pediatrics FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose. FUNDING: No external funding. POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose. 22 ROSS et al

2 ARTICLE Practitioners frequently make decisions for children based on oxygen saturations obtainedfrompulseoximetry.interventions such as supplemental oxygen, diuretics, or transfer to a higher level ofcarefrequently occur without an arterial blood gas (ABG). Pulse oximeter performance has an impact on clinical decisions. Pulse oximeters are developed to perform optimally in a range of oxyhemoglobin saturation from 70% to 100%. The US Food and Drug Administration (FDA) requires documentation of pulse oximeter accuracy defined as accuracy root mean squared (A rms ),3% with an equal number of samples in the decile range of 70% to 100% from adult volunteers through the standard ISO : As indicated in the FDA s document Pulse Oximeters Premarket Notification Submissions [510(k)s] 2 for devices intended for use with neonates, the FDA recommends performance reports using adult subjects. Additional convenience arterial samples obtained in neonates are recommended when the sensor is new or significantly changed compared with previous devices. It is unclear how well pulse oximeters perform when the majority of observations are in children in a hypoxemic range. Previous work in children has been limited by small samples of observations in a hypoxemic range. However, these earlier manuscripts indicate SpO 2 may systematically overestimate measured arterial oxygen saturation from ABG sampling. 3,4 The SpO 2 overestimation may also be dependent on location of measurement, 4,5 perfusion to the extremity where the pulse oximeter is located, and skin color. 6,7 The population of children with lower baseline oxygen saturations is growing. There are many children with cyanotic congenitalheartdisease(cchd)undergoing and surviving palliative procedures. In addition, practitioners frequently manage children with acutehypoxemicrespiratory failure (AHRF) without arterial catheters. 8 In these children, practitioners often increase ventilator support and fraction of inspired oxygen when the oxygen saturation falls out of an acceptable range (,87%). Although some manufacturers have developed pulse oximeters with hypoxemic measurements in mind (Masimo Blue Sensors, Nellcor LoSat Sensors), thesesensorsarenotroutineinmost hospitals. The primary objective of this study was to determine the performance of pulse oximetry for children in the range of 65% to 97% compared with arterial oxygen saturation measurements from CO-oximetry (SaO 2 ). To overcome limitations with a single measure of bias or precision over the entire range of pulse oximetry, the mean bias, local bias, precision, and A rms are reported. The secondary objective was to explore clinical scenarios in which pulse oximetry may be less reliable. METHODS Patients A prospective, observational study in 5 US multidisciplinary PICUs was conducted from August 2009 to October The participating PICUs were Children s Hospital Los Angeles, Penn State Children s Hospital, University of Virginia Children s Hospital, Monroe Carell Children s Hospital, and Cohen Children s Medical Center of New York. Patients were eligible if they were intubated, mechanically ventilated, had an arterial catheter, had SpO 2 values #97%, and were $37 weeks gestational age and,18 years. Patients were excluded if they were receiving extracorporeal membrane oxygenation or were not on a fully supported mode of ventilation. Continuous pulse oximeter recordings were standard of care in all PICUs. Patient demographics were obtained on enrollment and included age, race/ethnicity, gender, weight, and diagnosis. Patients were identified as to whether they had CCHD or AHRF. All participating PICUs had institutional review board approval with waiver of written consent. 9 Measurements The decision to obtain an ABG sample with CO-oximetry was left to the primary care team. The bedside provider was trained by a member of the research team before any data collection. Sensor cleanliness and position were verified before obtaining the ABG. The SpO 2 value was prospectively documented at the precise time the ABG was obtained (ABG/SpO 2 pair). ABG/SpO 2 pairs were not recorded if SpO 2 was.97% or there was endotracheal tube suctioning in the 10 minutes before or ventilator changes in the 30 minutes before the ABG. The ABG/SpO 2 pair was not recorded if the pulse oximeter value was not stable before the ABG or if there was concern about the waveform quality. For inclusion in the analysis, SaO 2 was measured using CO-oximetry. The blood gas machines used in the study were the ABL800 (Radiometer Medical Aps, Brønshøj, Denmark), Rapidlab 1265 (Siemens Healthcare, Erlangen, Germany), and Gem 3000 (Instrumentation Laboratory, Lexington, MA). Additional information recorded with each ABG/SpO 2 pair included temperature, capillary refill in the extremity with the sensor, hemoglobin, pulse oximeter type, end tidal carbon dioxide, and degree of ventilator support. If the patient had CCHD with a physiology that was dependent on flow through a patent ductus arteriosus and there was a difference in pre- and postductal oxygen saturation, the protocol required that the pulse oximeter sensor and the arterial line were on the same side of the ductus. Ventilator information included peak inspiratory pressure, positive end expiratory pressure, pressure support, rate, exhaled tidal volume, mean PEDIATRICS Volume 133, Number 1, January

3 airway pressure, fraction of inspired oxygen, and mode. Hemoglobin values were recorded from laboratory samples, and when unavailable, they were obtained from the ABG. Masimo pulse oximeters withthelcnslineofprobes(masimo Corporation, Irvine, CA) were used by 2 PICUs and Nellcor pulse oximeters with the OxiMax line of probes (Covidien-Nellcor, Boulder, CO) were used by 2 PICUs. One PICU used Masimo oximeters with the Nellcor OxiMax line of disposable probes. Terms To describe pulse oximeter performance, itishelpfultoreviewafewstatisticalterms commonly used: bias, precision, accuracy, and A rms. Bias is the SpO 2 SaO 2.SaO 2 as the reference standard from an ABG measured via CO-oximetry. Mean bias is the average SpO 2 SaO 2 using all study observations, over the entire range, and is influenced by where the preponderance of pulse oximetry measurements lies. Local bias is mean SpO 2 SaO 2 over a specific range of SpO 2. Precision is typically 1 SD above and below the mean bias, describing how much random error is in the data. Methods to calculate precision require the bias to be normally distributed, which may not always be true. The limits of agreement are usually taken as 1.96 times the SD unless there is correction for repeated measures. The term accuracy is a measure of how far a value is from a reference standard. However, pulse oximeter companies generally present A rms,whichis required by agencies that regulate pulse oximeters. The A rms combines the components of bias and precision controlling for the number of samples obtained. A rms of #3% is required by the FDA. Analysis The primary objective of this study was to evaluate the accuracy of simultaneous samples of SpO 2 compared with SaO 2 obtained by CO-oximetry throughout a range of SpO 2 values. Additional objectives were to identify variables that may affect the bias of SpO 2 compared with SaO 2 in the hypoxemic range. Statistical analysis was performed by using Stata version 10 (StataCorp, College Station, TX) and Statistica version 9 (Statsoft, Tulsa, OK). Overall bias was assessed with a scatter plot of SpO 2 against SaO 2. Local bias was assessed via a box-and-whisker plot examining the difference between SpO 2 and SaO 2 in 7 SpO 2 ranges. To explore inaccuracy, a bar graph was generated of counts of ABG/SpO 2 pairs in which the absolute value of (SpO 2 SaO 2 )is#3% and.3% as a function of SpO 2 range. Precision was reported with SD. However, because residuals were not normally distributed, median and interquartile range of (SpO 2 SaO 2 ) as a whole and for each SpO 2 range were reported. A rms was calculated from the formula sffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi + N i¼1 A rms ¼ ðspo 2i 2 SaO 2i Þ 2 n as a whole and for each SpO 2 range. To evaluate the potential influence of clinical variables on pulse oximetry bias, the ABG/SpO 2 pairs were separated into groups based on absolute value of the bias of #3% or.3%. This separation was used to perform a multivariate logistic regression analysis using a mixed model to examine the effect of other potential confounding variables and to control for repeated measures per patient. The confounding variables included disease category, gender, oximeter and sensor type, capillary refill in the extremity with the pulse oximeter, hemoglobin, temperature, and degree of ventilator support. Confounders were considered for model inclusion if they had a univariate relationship with the outcome (P,.2) or if there was strong biologic plausibility to suspect that they may influence the relationship between SpO 2 and SaO 2 (eg, capillary refill). Finally, to explore whether multiple measurements per subject biased the results, data were filtered to randomly extract a single ABG/SpO 2 pair from each patient that fell within the SpO 2 ranges previously identified. Values for bias and precision (SD) using only 1 sample per patient per range were calculated and compared with the entire data set. RESULTS Two hundred twenty-five children were enrolled with 1980 ABG/SpO 2 pairs. The median number of ABG/SpO 2 pairs per patient was 5, interquartile range (2 10), range (1 110). Demographics separated by CCHD or AHRF are shown in Table 1. The source and results of the ABG/SpO 2 pairs including ventilation information are shown in Table 2. The children with CCHD were younger, weighed less, had lower oxygen saturations, had higher hemoglobin values, and required less ventilator support compared with the group with AHRF (all Ps,.001). The 122 children with CCHD accounted for 1175 ABG/SpO 2 pairs with a median SpO 2 of 82% and a median SaO 2 of 77%, with 82% of the ABG/SpO 2 pairs having a SpO 2 #90%. The 103 children with AHRF accounted for 805 ABG/SpO 2 pairs with a median SpO 2 of 95% and a median SaO 2 of 94%, with 14% of the ABG/SpO 2 pairs having a SpO 2 #90%. Entire Range of SpO 2 Values for SpO 2 are plotted against SaO 2 for all ABG/SpO 2 pairs in Fig 1. A total of 1304 of the 1980 samples (66%) had a positive bias (SpO 2 SaO 2. 0). Although the data were not normally distributed, mean and SD are presented to be consistent with other studies. For the entire SpO 2 range 65% to 97% the mean bias was 3.3%, median 2%, the precision (SD) 5.6%, interquartile range (0% 6%), and the A rms 6.5% (Table 3). 24 ROSS et al

4 ARTICLE TABLE 1 Patient Demographics Smaller Ranges of SpO 2 There were significant differences in bias, precision (SD), and accuracy based on SpO 2 range. The local bias (SpO 2 SaO 2 ) was lowest in the SpO 2 ranges of 65% to 70% and 96% to 97% with median values of 0% and greatest in the SpO 2 range of 81% to 85% with a median value of 6% (Fig 2). Precision (SD) and A rms were worst in the SpO 2 range of 81% to 85%, with poor accuracy in all ranges,91% (Table 3). CCHD (n = 122) AHRF (n = 103) P Age, mo, (interquartile range) 1 (1 3) 37 (5 140),.001 Weight, kg, (interquartile range) 3.5 (3 4.6) 14.8 (5 36),.001 Gender, male, n (%) 74 (61) 63 (62).95 Race/ethnicity, n (%) African American 8 (7) 12 (12).20 Hispanic 59 (48) 35 (34) White 47 (39) 47 (45) Asian 4 (3) 3 (3) Other 4 (3) 6 (6) Differences between groups analyzed by Mann-Whitney U Test, x2 test or observed/expected x2 test. TABLE 2 Source and Results of ABG/SpO 2 Pairs Including Ventilation CCHD (n = 1175) AHRF (n = 805) P Oximeter-Sensor Masimo-Masimo 982 (83.6%) 578 (71.8%),.001 Nellcor-Nellcor 146 (12.4%) 180 (22.4%) Masimo-Nellcor 47 (4%) 47 (5.8%) SpO 2 % 82 (78 88) 95 (92 96),.001 SaO 2 % 77 (72 83) 94 (90 96),.001 ph 7.39 ( ) 7.40 ( ).24 PaO 2, mm Hg 42 (38 49) 69 (60 83),.001 PaCO 2, mm Hg 45 (40 52) 55 (45 69),.001 Base excess 0 (0 0) 0 (0 0) 1 FiO ( ) 0.6 ( ),.001 Capillary refill (s) 3 (3 3) 3 (1 3),.001 Hemoglobin (g/dl) 15 (14 16) 11 (10 13),.001 Temperature C 37 (37 37) 37 (37 37).76 Conventional ventilation n = 1168 n = 611 End tidal carbon dioxide (mm Hg) 32 (25 37) 37 (27 45),.001 Peak inspiratory pressure (cm H 2 O) 24 (20 26) 30 (24 36),.001 Positive end-expiratory pressure (cm H 2 O) 5 (4 5) 8 (5 10),.001 Mean airway pressure (cm H 2 O) 9 (8 11) 15 (11 20),.001 Tidal volume (ml/kg) 10 (8 10) 8 (7 10),.001 Pressure support (cm H 2 O) 10 (10 10) 10 (5 11),.001 Ventilator rate (breaths/min) 20 (15 25) 20 (16 25).89 High frequency oscillatory ventilation n =7 n = 194 Mean airway pressure (cm H 2 O) 28 (21 31) 30 (25 33).20 Amplitude 51 (48 54) 60 (50 65).07 Frequency (Hz) 9 (9 9) 8 (6 9).04 Number and percentage of oximeter-sensor combinations are calculated by column. Data (not normally distributed) are presented as median (interquartile range). Differences between groups analyzed by Mann-Whitney U test or observed/ expected x2 test. FiO 2, fraction of inspired oxygen. The data were filtered to randomly extract a single ABG/SpO 2 pair from each patient that fell within the SpO 2 ranges. Five hundred twenty-six ABG/SpO 2 pairs remained with a mean bias of 2.8%, median 2%, precision (SD) 5.6%, interquartile range ( 1% to 6%), and A rms was 6.3% (nearly identical to values including repeated measurements). Findings were also similar within each of the SpO 2 ranges (analysis not shown). Multivariate Modeling The ABG/SpO 2 pairs were separated into 2 groups based on whether the absolute value of the bias was #3% or.3% (Table 4). For ABG/SpO 2 pairs in which the bias was.3%, children with CCHD accounted for 78% of the samples (719 of 922) compared with children with AHRF (P,.001). The proportion of instances when the bias is.3% is highest in the midrange of SpO 2 (75% 90%; Fig 3). From multivariate modeling, variables associated with higher likelihood of bias.3% include CCHD, prolonged capillary refill, and having a SpO 2 between 81% to 85%, 86% to 90%, or 91% to 95% (compared with a SpO 2 of 96% to 97%; Table 5). Variables associated with a lower likelihood of bias were African American race/ethnicity, male gender, and the combination of Masimo oximeter with a Nellcor sensor. After controlling for these variables, mean airway pressure, hemoglobin, PICU site, temperature, fraction of inspired oxygen, age,2 months, other races/ethnicity, and other oximeter combinations did not contribute to the model. Because the majority of observations in the lower ranges of SpO 2 came from children with CCHD, a second multivariate model was performed restricted to only the subgroup of children with CCHD. Overall results were similar with a higher likelihood of bias associated with prolonged capillary refill and SpO 2 ranges of 81% to 85% and 86% to 90%. Furthermore, a lower likelihood of bias was associated with African American race/ethnicity and male gender. DISCUSSION There is significant variability in the bias, precision (SD) and accuracy of pulse oximetry as a function of SpO 2. SpO 2 on average overestimates SaO 2 measured with CO-oximetry. This local bias is most positive in the SpO 2 range PEDIATRICS Volume 133, Number 1, January

5 FIGURE 1 SpO 2 plotted against SaO 2 for all ABG/SpO 2 pairs. The line indicates the line of equality between SpO 2 and SaO 2. Bubble size indicates number of values in that range. A total of 1304 of the 1980 samples (66%) lie above the line, indicating a positive bias for SpO 2 measurements. TABLE 3 Percent Difference of SpO 2 SaO 2 for Each ABG/SpO 2 Pair SpO 2 Range % Count Median Bias % IQR Mean Bias % SD % A rms % Entire range to to to to to to to to Presented are count of ABG/SpO 2 pairs, median bias, interquartile range (IQR), mean bias, SD, and A rms presented for SpO 2 65% to 97% and subset ranges. between 81% to 85%, although it is present in the SpO 2 range of 76% to 90%. The precision (SD) and accuracy are also poor in this range. Although the median bias is low in the SpO 2 range from 65% to 75%, there is poor precision (SD) and accuracy. This variability in bias, precision, and accuracy remains after controlling for capillary refill, diagnosis, pulse oximeter, gender, and race/ethnicity. These findings may have significant clinical implications. For example, if the SpO 2 is measured at 85%, on average the SaO 2 would be 79% and 50% of the time the SaO 2 would lie between 75% and 83%. However, to achieve 95% certainty, SaO 2 values would lie between 64% and 89%. In contrast, if the SpO 2 is measured at 94%, on average the SaO 2 would be 93% and 50%ofthetimetheSaO 2 would lie between 90% and 95% and 95% of the time the SaO 2 would lie between 89% and 99%. In the lowest SpO 2 range of 65% to 70%, the median bias is close to zero, but the poor precision (SD) and accuracy could affect clinical care. Physicians caring for CCHD patients often make different treatment decisions based on whether the SpO 2 is 65% vs 70%. Improved accuracy in this range could help decision-making. The increased bias and poor precision in the lower SpO 2 range may add insight into recent findings from neonatology demonstrating potential harm with lower oxygen saturations Three large multicenter randomized trials have targeted ranges of SpO 2 to prevent retinopathy of prematurity. Two of the 3 trials demonstrated increased mortality in the oxygen saturation group from 85% to 89%, compared with 91% to 95%. 10,12 The increased bias when SpO 2 is,90% may result in SaO 2 values that are much lower than anticipated. The multivariate model shows that pulse oximetry performs less well in children with CCHD and prolonged capillary refill. Children with CCHD were thelargestproportioninthespo 2 range from 81% to 85%, although this range remained the most likely for bias even when restricting the analysis only to children with CCHD. Therefore, it appears the inaccuracy is most related to the range of SpO 2 and not the presence of CCHD. Prolonged capillary refill makes physiologic sense because greater bias is anticipated with poorer 26 ROSS et al

6 ARTICLE FIGURE 2 Box plot of (SpO 2 SaO 2 ) by SpO 2 range increments for all patients. The number of ABG/SpO 2 pairs in each increment is above the whisker. Bias varies throughout the SpO 2 range with the largest bias in 81% to 85% SpO 2 range. The bias is small for SpO 2 $91%. perfusion. 3 Age,2 months showed a univariate effect, but this was not supported by the regression model. Age was meant as a surrogate for fetal hemoglobin, which may also be partially captured by other elements of the multivariate model. African American race/ethnicity and male gender were associated with lower likelihood of bias of the pulse oximeter. It is unclear what conclusions can be drawn from this. Race/ethnicity but not degree of skin color was recorded. There is no clear biological mechanism in which gender should have an impact on pulse oximetry performance. It is possible these are surrogates for an unmeasured confounding variable. The findings of this study are consistent with other, smaller studies. Das et al 5 in 2010 studied pulse oximeter bias based on sensor location. Unfortunately, only 8 children had oxygen saturations,90%. However, in their small sample size, SpO 2 wasalwaysgreater than SaO 2. Sedaghat-Yazdi et al 4 in 2008 studied pulse oximeter bias based on sensor location. However, only 24 samples had SaO 2,90%. In 2004, Torres et al 3 showed poor pulse oximeter accuracy with 77 SaO 2 samples,90%. Our study echoes these findings and has the largest sample size to date by an order of magnitude. Although pulse oximeters are marketed as meeting standards of accuracy throughout a range of oxygen saturations, this study highlights the need for manufacturers to present more data than the A rms for the entire range. Because mean bias and A rms will be influenced by large number of samples with SpO 2 values.91%, where pulse oximeters perform best, a single number for accuracy does not tell the entire picture. Furthermore, accuracy of pulse oximetry algorithms are often demonstrated using adult healthy volunteers breathing a hypoxic gas mixture, which is not the clinical environment in which they are used. The local bias, precision (SD), and accuracy values presented are much larger than anticipated. The data for this study were acquired in a clinical setting, in the context of a reasonably controlled research study. Accuracy of pulse oximetry algorithms are generally demonstrated in a laboratory setting using adult healthy volunteers breathing a hypoxic gas mixture. This study was unable to meet the rigorous conditions of a research laboratory setting, 13 but the findings highlight the real-world clinical application of this scenario. Although it is not reasonable to generate hypoxia in children to produce an improved algorithm for pulse oximetry, there are pediatric cardiac surgery centers with large numbers of patients with CCHD. Perhaps future development could occur with a population such as this to generate algorithms that are more accurate for all children. There are limitations to this study. First, the multicenter nature of the study increases generalizability, but the results may be confounded by institutional variation. For example, in 1 hospital, a sensor was used that was different from the manufacturer of the oximeter machine, making it difficult to determine the source of inaccuracy. However, this is a real-world situation, and results from that hospital were not large enough to skew the overall trend. Subgroup analysis by pulse oximeter PEDIATRICS Volume 133, Number 1, January

7 TABLE 4 Absolute Value of (SpO 2 SaO 2 ) Difference as #3% or.3% by Condition Condition Absolute Value of (SpO 2 SaO 2 ) Difference P #3% (n = 1058).3% (n = 922) CCHD 456 (43.1%) 719 (78.0%),.001 AHRF 602 (56.9%) 203 (22.0%) Age,2 mo 453 (42.8%) 513 (55.6%), mo 605 (57.2%) 409 (44.4%) Gender, male 802 (75.8%) 584 (63.3%),.001 Race/Ethnicity African American 201 (19.0%) 86 (9.3%),.001 Hispanic 292 (27.6%) 282 (30.6%) White 484 (45.7%) 463 (50.2%) Asian 39 (3.7%) 50 (5.4%) Other 40 (3.8%) 41 (4.4%) Unknown 2 (0.2%) 0 Capillary refill (s) (37.4%) 221 (24.0%), (49.6%) 540 (58.6%) (10.9%) 127 (13.8%) 5 19 (1.8%) 22 (2.1%) 6 3 (0.3%) 12 (1.3%) PICU (48.5%) 538 (58.3%), (7.0%) 20 (2.2%) (25.8%) 236 (25.6%) 4 79 (7.5%) 62 (6.7%) (11.2%) 66 (7.2%) Oximeter-sensor combination Masimo-Masimo 786 (74.3%) 774 (83.9%),.001 Nellcor-Nellcor 198 (18.7%) 128 (13.9%) Masimo-Nellcor 74 (7.0%) 20 (2.2%) SpO 2 range (1.8%) 22 (2.4%), (4.9%) 68 (7.4%) (13.3%) 178 (19.3%) (8.5%) 246 (26.7%) (10.4%) 143 (15.5%) (33.6%) 184 (20.0%) (27.4%) 71 (7.7%) Data are count of ABG/SpO 2 pairs (percent total). Differences between groups analyzed by x2 test or observed/expected x2 test. FIGURE 3 Count of ABG/SpO 2 pairs by absolute value of the bias #3% or.3% over SpO 2 range. The proportion of observation varies over the range with an increased number at higher SpO 2. The effect of local bias would be missed if the entire range were presented as a single number. TABLE 5 Multivariate Model Controlling for Patient Effect Variable Coefficient P CCHD 1.82,.001 Capillary refill 0.26,.001 Male gender Race/ethnicity White Baseline NA African American Hispanic NS Asian NS Other NS Oximeter-Sensor Masimo-Masimo Baseline NA Masimo-Nellcor Nellcor-Nellcor 0.04 NS SpO 2 range 96% 97% Baseline NA 65% 70% 0.23 NS 71% 75% 0.16 NS 76% 80% 0.05 NS 81% 85% % 90% 1.08, % 95% 0.75,.001 Entire group of patients. Positive values for the coefficient imply higher likelihood of outcome (bias.3%). Variables that were considered but not included are mean airway pressure, hemoglobin, PICU site, temperature, and age,2 mo. NA, not applicable brand was not performed because the majority of samples were measured with 1 oximeter brand. However, there was similar SpO 2 overestimation in the second manufacturer, and in that subgroup, this sample size is as large as any previously reported. Moreover, pulse oximetry type (except the combination of Masimo oximeter and Nellcor sensor) was not significant in the multivariate model. A second limitation is that the data were collected using a waiver of consent. In turn, no patient-identifying information was retained, preventing us from gathering variables not initially included in the study. Such examples include perfusion index, location of pulse oximeter probe, amount of fetal hemoglobin, presence of other hemoglobin species, use of inotropic medications, presence of a patent ductus arteriosus, and pulse pressure. These are potential confounding variables that were not captured. These areas should be investigated in future studies with pulse oximetry. 28 ROSS et al

8 ARTICLE A third limitation is that fetal hemoglobin was not measured. Pulse oximeter algorithms are generated from adult volunteers with the assumption of 2 types of hemoglobin: oxy and deoxyhemoglobin. They may not perform well with carboxyhemoglobin, methemoglobin, or possibly fetal hemoglobin. There are limited studies showing the performance of pulse oximeters in the presence of fetal hemoglobin, 14,15 with conflicting results. Although it is possible that fetal hemoglobin has an impact on pulse oximetry it is unlikely to explain all of the findings, given that results are similar when restricting to only older patients (Supplemental Information). Furthermore, there was no difference in oxygen dissociation curves based on age #2 months or.2 months (Supplemental Information), supporting the idea that the findings are not solely explained by fetal hemoglobin. CONCLUSIONS Pulse oximeters appear to be accurate against CO-oximetry in a higher SpO 2 range such as.91%. However, in the lower SpO 2 range (76% 90%), the local bias (SpO 2 SaO 2 )is 5% and the precision (SD) and accuracy are poor when SpO 2 is,90%. The manufacturers of these devices should improve algorithms in this range. ACKNOWLEDGMENTS The authors thank those people who organized and participated in the research study: Comparison of SpO 2 to PaO 2 Based Markers of Lung Disease Severity for Children With Acute Lung Injury, which provided the data for this article: Neal J. Thomas, MD, MsC, Vani Venkatachalam, MD, Jason P. Sciememe, MD, Ty Berutti, MD, MS, James B. Schneider, MD, Douglas F. Willson, MD, Mark W. Hall, MD, Debbie Spear, Jill Raymond, Christine Traul, Jeff Terry, and Paul Vee. REFERENCES 1. International Organization for Standardization (ISO). Particular requirements for basic safety and essential performance of pulse oximeter equipment (ISO ). Geneva, Switzerland: ISO; Center for Devices and Radiological Health. Pulse oximeters premarket notification submissions [510(k)s]. (document issued March 4, 2013). Food and Drug Administration; Available at: Devices/DeviceRegulationandGuidance/ GuidanceDocuments/UCM pdf. Accessed November 1, Torres A Jr, Skender KM, Wohrley JD, et al. Pulse oximetry in children with congenital heart disease: effects of cardiopulmonary bypass and cyanosis. J Intensive Care Med. 2004;19(4): Sedaghat-Yazdi F, Torres A Jr, Fortuna R, Geiss DM. Pulse oximeter accuracy and precision affected by sensor location in cyanotic children. Pediatr Crit Care Med. 2008;9(4): Das J, Aggarwal A, Aggarwal NK. Pulse oximeter accuracy and precision at five different sensor locations in infants and children with cyanotic heart disease. Indian J Anaesth. 2010;54(6): Bickler PE, Feiner JR, Severinghaus JW. Effects of skin pigmentation on pulse oximeter accuracy at low saturation. Anesthesiology. 2005;102(4): Feiner JR, Severinghaus JW, Bickler PE. Dark skin decreases the accuracy of pulse oximeters at low oxygen saturation: the effects of oximeter probe type and gender. Anesth Analg. 2007;105(suppl 6):S18 S23 8. Khemani RG, Markovitz BP, Curley MA. Characteristics of intubated and mechanically ventilated children in 16 pediatric ICUs. Chest. 2009;136: Khemani RG, Thomas NJ, Venkatachalam V, et al; Pediatric Acute Lung Injury and Sepsis Network Investigators (PALISI). ComparisonofSpO2toPaO2basedmarkersof lung disease severity for children with acute lung injury. Crit Care Med. 2012;40 (4): Carlo WA, Finer NN, Walsh MC, et al; SUPPORT Study Group of the Eunice Kennedy Shriver NICHD Neonatal Research Network. Target ranges of oxygen saturation in extremely preterm infants. N Engl J Med. 2010;362(21): Schmidt B, Whyte RK, Asztalos EV, et al; Canadian Oxygen Trial (COT) Group. Effects of targeting higher vs lower arterial oxygen saturations on death or disability in extremely preterm infants: a randomized clinical trial. JAMA. 2013;309(20): The BOOST II United Kingdom, Australia, and New Zealand Collaborative GroupsOxygen saturation and outcomes in preterm infants. N Engl J Med. 2013;368(22): Batchelder PB, Raley DM. Maximizing the laboratory setting for testing devices and understanding statistical output in pulse oximetry. Anesth Analg. 2007;105(suppl 6): S85 S Shiao SY. Effects of fetal hemoglobin on accurate measurements of oxygen saturation in neonates. J Perinat Neonatal Nurs. 2005;19(4): Rajadurai VS, Walker AM, Yu VY, Oates A. Effect of fetal haemoglobin on the accuracy of pulse oximetry in preterm infants. J Paediatr Child Health. 1992;28(1):43 46 PEDIATRICS Volume 133, Number 1, January

9 Accuracy of Pulse Oximetry in Children Patrick A. Ross, Christopher J.L. Newth and Robinder G. Khemani Pediatrics 2014;133;22 DOI: /peds originally published online December 16, 2013; Updated Information & Services Supplementary Material References Subspecialty Collections Permissions & Licensing Reprints including high resolution figures, can be found at: Supplementary material can be found at: DCSupplemental This article cites 12 articles, 0 of which you can access for free at: This article, along with others on similar topics, appears in the following collection(s): Hematology/Oncology y:oncology_sub Blood Disorders rders_sub Cardiology _sub Cardiovascular Disorders ular_disorders_sub Information about reproducing this article in parts (figures, tables) or in its entirety can be found online at: Information about ordering reprints can be found online: Pediatrics is the official journal of the American Academy of Pediatrics. A monthly publication, it has been published continuously since. Pediatrics is owned, published, and trademarked by the American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk Grove Village, Illinois, Copyright 2014 by the American Academy of Pediatrics. All rights reserved. Print ISSN:.

10 Accuracy of Pulse Oximetry in Children Patrick A. Ross, Christopher J.L. Newth and Robinder G. Khemani Pediatrics 2014;133;22 DOI: /peds originally published online December 16, 2013; The online version of this article, along with updated information and services, is located on the World Wide Web at: Pediatrics is the official journal of the American Academy of Pediatrics. A monthly publication, it has been published continuously since. Pediatrics is owned, published, and trademarked by the American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk Grove Village, Illinois, Copyright 2014 by the American Academy of Pediatrics. All rights reserved. Print ISSN:.